An electrolyte-entrapping liposome was immobilized on an Au electrode to design and develop an immobilized-liposome sensor (ILS) system for the detection of the damage of proteins. Three kinds of proteins, such as bovine carbonic anhydrase, lysozyme and chitosanase, were used as model analytes. The proteins treated by a denaturant (guanidium hydrochloride, GuHCl) were applied to the ILS analysis, resulting that the significant electrical signals could effectively be detected due to the interaction between the liposome and GuHCl-denatured protein. The diffusion currents normalized by protein concentrations were linearly correlated with local hydrophobicity of proteins evaluated by the conventional aqueous two-phase partitioning method. The ILS system can, therefore, be utilized as a useful tool for an on-line monitoring to conformational changes of proteins.